Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Front Immunol. 2020 Jan 10;10:2997. doi: 10.3389/fimmu.2019.02997. eCollection 2019.
It has been almost a decade since the 2009 influenza A virus pandemic hit the globe causing significant morbidity and mortality. Nonetheless, annual influenza vaccination, which elicits antibodies mainly against the head region of influenza hemagglutinin (HA), remains as the mainstay to combat and reduce symptoms of influenza infection. Influenza HA is highly antigenically variable, thus limiting vaccine efficacy. In addition, the variable HA head occupies the upper strata of the immunodominance hierarchy, thereby clouding the antibody response toward subdominant epitopes, which are usually conserved across different influenza strains. Isolation of monoclonal antibodies from individuals recognizing such epitopes has facilitated the development of recombinant vaccines that focus the adaptive immune response toward conserved, protective targets. Here, we review some significant leaps in recombinant vaccine development, which could possibly help to overcome B cell and antibody immunodominance and provide heterosubtypic immunity to influenza A virus.
自 2009 年甲型流感病毒大流行袭击全球以来,已经过去了将近十年,这场大流行导致了大量的发病率和死亡率。尽管如此,每年接种流感疫苗仍然是对抗和减轻流感感染症状的主要方法,因为流感疫苗主要诱导针对流感血凝素 (HA) 头部的抗体。流感 HA 具有高度的抗原变异性,因此限制了疫苗的效果。此外,可变的 HA 头部占据了免疫优势层次结构的上层,从而掩盖了针对亚显性表位的抗体反应,这些表位通常在不同的流感株中是保守的。从识别这些表位的个体中分离出单克隆抗体,促进了重组疫苗的发展,这些疫苗将适应性免疫反应集中在保守的、保护性的靶标上。在这里,我们回顾了重组疫苗开发的一些重要进展,这些进展可能有助于克服 B 细胞和抗体的免疫优势,并为甲型流感病毒提供异源免疫。